CHARACTERIZATION OF TSH ANTAGONIST ACTIVITY IN THE SERUM OF PATIENTS WITH THYROID DISEASE

The ability of sera from patients with thyroid disease to block TSH stimulation of cyclic AMP release from isolated porcine thyroid cells has been assessed and the blocking activity characterized. TSH receptor binding activity was also measured. No blocking or receptor binding activity was detectable in patients with primary myxoedema (n = 23), Hashimoto's disease (n = 11), multinodular goitre (n = 6), or rheumatoid arthritis (n = 10). However, analysis of sera from 23 patients (out of an initial screen of 110 patients) with treated Graves' disease which did not stimulate cyclic AMP production in the bioassay showed that two of these sera contained powerful blocking and receptor binding activity. Both these patients had been treated with 131I. Analysis of the two sera by gel filtration on Sephadex G-200 indicated that blocking and TSH receptor binding activity were associated only with the IgG fraction. Digestion of the IgG with pepsin followed by reduction showed that both (Fab)2 and Fab fragments contained high levels of blocking and binding activity. Antibody divalency was not necessary therefore for TSH antagonist activity. However, our studies suggest that autoantibodies of this type with TSH antagonist activity do not occur frequently in patients from the Cardiff region with primary myxoedema, Hashimoto's or treated Graves' disease.     

Implications of volume of nodal metastasis in patients with adenocarcinoma of the prostate

We divided 73 cases of pelvic nodal metastases from prostatic cancer into subgroups based upon the volume and extent of nodal disease. Of the patients with gross nodal disease 15 per cent survived 5 years without progression compared to 27 per cent of those with microscopic involvement of more than 1 node and 44 per cent with a single positive node. On the other hand, 52 per cent of the patients with gross disease died of prostatic cancer within 5 years compared to 37 per cent of those with multiple microscopic nodes and 28 per cent with a single node. Although other variables also influence prognosis, the differences in survival demonstrable within these subgroups may have important implications regarding selection of therapy and interpretation of treatment results.     

Lethal epidermolytic epidermolysis bullosa: a new autosomal recessive type of epidermolysis bullosa

A distinctive form of epidermolysis bullosa is reported among several members of a large Sudanese family. Although on ultrastructural grounds this appears to be simplex type, it is inherited as an autosomal recessive trait and is associated with a high mortality.     

Comparing professional and patient outcomes for the same episode of care.

Following an acute hospital admission, patients' perceptions of the acceptability of their own outcomes were compared with professionally derived outcomes of care developed for the same patients by nurses. Professional opinion was obtained from the Nursing Practice--Casemix and Outcomes Project undertaken by the Sydney Metropolitan Teaching Hospitals Nursing Consortium, where patient outcomes were classified by nurses into three groups: Outcomes Acceptable; Outcomes Not Acceptable but Justified and Outcomes Not Acceptable and Not Justified. Fifteen male patients in the present study discussed their outcomes following recent orthopaedic surgery at a series of focus groups organised according to the three outcome categories. Findings from the study showed the majority of patients were satisfied with their outcomes. Patient agreement with nurses regarding the acceptability of outcomes was highest for patients from the Outcomes Acceptable group and lowest for those from the Outcomes Not Acceptable and Not Justified group. This work is significant in that it is one of the first nursing studies to compare outcomes developed by practitioners for a particular group of patients with actual outcomes experienced by the same group of patients.     

Longitudinal effects of pregnancy on the pharmacokinetics of theophylline

Summary The effects of pregnancy on the disposition of theophylline were assessed in 10 patients throughout pregnancy and post-partum. The clearance relative to total theophylline concentrations was only slightly affected during the first two trimesters (2.61±0.63 l/h and 2.85±1.05 l/h), while a statistically significant reduction was evident late in pregnancy (2.05±0.49 l/h). Post-partum clearance values (2.16±2.81 l/h) suggest an ongoing suppression relative to pre-pregnancy levels. A similar pattern was evident with clearance values based on free theophylline plasma concentrations (p=0.12). Absolute volume of distribution increased in concert with gestation, suggesting that theophylline partitions into the enlarged tissue spaces. In addition, theophylline binding to plasma proteins decreased, albeit insignificantly, during the second (fraction bound=29%) and third (32%) trimesters compared to post-partum values (41%). Increases in half-life during the third trimester (13.00±2.31 h vs 9.53±3.53 h post-partum) were highly significant. This change reflects the net effect of reduced clearance and increased distribution. Breast feeding had no effect on the disposition of theophylline, although the transfer of this compound into breast milk was confirmed.     

Storage of pooled platelet concentrates. In vitro and in vivo analysis

The use of sterile connecting devices will permit up to 5-day storage of pooled platelet concentrates (PCs). However, there are no data evaluating long-term storage of PCs pooled from multiple donors. Four units of ABO-compatible or -incompatible PCs were pooled and stored in single 300-ml PL-732 storage bags for up to 5 days. Results of in vitro assays showed acceptable storage values regardless of the ABO types in the pool. Pool pH on Day 5 was 6.83 +/- 0.3 (mean +/- 1 SD). The in vitro storage characteristics were comparable to those of unpooled age-matched platelets reported previously from our laboratory. For in vivo studies, 4-unit pools of ABO-compatible random-donor PCs stored for up to 96 hours in 1000-ml PL-732 bags were transfused into patients who were thrombocytopenic due to bone marrow failure, and the correct count increments (CCI) were determined. In vivo results showed a mean 1-hour CCI of 11,368 +/- 5824 for the pooled stored platelets and 7819 +/- 5189 for unpooled controls (p greater than 0.05). To evaluate the possibility that passenger lymphocytes in the concentrates would generate mixed lymphocyte reactions (MLR) in the pooling bag during storage, lymphocytes were studied over 5 days of storage by the use of monoclonal antibodies against activated T-cell markers and by 3H thymidine uptake. Results failed to show evidence of either the generation of activated T-cell markers or the uptake of 3H thymidine.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of azelastine and some other antiasthmatic and antiallergic drugs on calmodulin and protein kinase C

The antiallergic and antiasthmatic drug, azelastine, interacts strongly with calmodulin (but not bovine serum albumin) as determined by an indirect assay; it also moderately inhibited the Ca²⁺-calmodulindependent enzyme bovine brain phosphodiesterase. Ketotifen was less active than azelastine in both assays of calmodulin reactivity and both drugs were less active than the recognized calmodulin inhibitor, W-7. Neither azelastine nor ketotifen had any inhibitory effect on the Ca²⁺- and phospholipid-dependent protein kinase C. A number of other commonly employed antiallergic and antiasthmatic drugs were essentially inactive in the calmodulin assays and had no or marginal inhibitory effect on protein kinase C.     

Validity of the Developed Arabic Multidimensional Health Assessment Questionnaire for use in standard clinical care of patients with rheumatic diseases

Objective: To assess the validity, reliability and comprehensibility of the Developed Arabic Multidimensional Health Assessment Questionnaire (Arabic‐MDHAQ) for use in standard clinical care of patients with rheumatic diseases. Methods: The multidimensional questionnaire was developed on a one‐page sheet. One side includes 10 activities of daily living (Arabic HAQII), four items to assess psychological distress, duration of morning stiffness as well as visual analogue scales for pain, global status, and fatigue. The other side includes review of the systems, falls and cardiovascular risk assessment, the rheumatology attitudes index to assess the psychological construct of helplessness and self‐report of joint counts. The questionnaire was completed by consecutive patients with various rheumatic diseases including 85 with rheumatoid arthritis, 57 with fibromyalgia, 57 with osteoarthritis, 18 with psoriatic arthritis and 11 with ulcerative colitis. Results: The test was reliable as demonstrated by a high standardized alpha‐value and minimal changes recorded in the second from the first test. The Developed Arabic‐MDHAQ correlated significantly with clinical parameters of disease activity as well as inflammatory markers. Changes in both functional and psychological assessment scores showed variation with diseases. The Arabic health assessment questionnaire II (functional disability) was significantly correlated with the original Arabic‐HAQ. The psychological assessment items in the Arabic‐MDHAQ were significantly correlated with depression as well as anxiety scores as demonstrated by Hamilton scales for depression and anxiety (P < 0.001). The Arabic‐MDHAQ showed also a high degree of comprehensibility (92.9%). Conclusion: The Developed Arabic‐MDHAQ is a reliable and valid instrument for assessment of Arabic patients suffering from rheumatic diseases. Being short, rapid and comprehensive, this adds more to its applicability. The data support the value of completion of the simple 2‐page patient questionnaire, which provides a quantitative written documented record by the patient, at each visit to a rheumatologist.